Verbal memory is linked to average oxygen saturation during sleep, not the apnea-hypopnea index nor novel hypoxic load variables.

INTRODUCTION: The apnea-hypopnea index (AHI) is the current diagnostic parameter for diagnosing and estimating the severity of obstructive sleep apnea (OSA). It is, however, poorly associated with the main clinical symptom of OSA, excessive daytime sleepiness, and with the often-seen cognitive decline among OSA patients. To better evaluate OSA severity, novel hypoxic load parameters have been introduced that consider the duration and depth of oxygen saturation drops associated with apneas or hypopneas. The aim of this paper was to compare novel hypoxic load parameters and traditional OSA parameters to verbal memory and executive function in OSA patients. METHOD: A total of 207 adults completed a one-night polysomnography at sleep laboratory and two neuropsychological assessments, the Rey Auditory Verbal Learning Test and Stroop test. RESULTS: Simple linear regression analyses were used to evaluate independent associations between each OSA parameter and cognitive performance. Associations were found between immediate recall and arousal index, hypoxia <90 %, average SpO2 during sleep, and DesSev100+RevSev100. Total recall was associated with all OSA parameters, and no associations were found with the Stroop test. Subsequently, sex, age, and education were included as covariates in multiple linear regression analyses for each OSA parameter and cognitive performance. The main findings of the study were that average SpO2 during sleep was a significant predictor of total recall (p < .007, ß = -.188) with the regression model explaining 21.2 % of performance variation. Average SpO2 during sleep was also a significant predictor of immediate recall (p < .022, ß = -.171) with the regression model explaining 11.4 % of performance variation. Neither traditional OSA parameters nor novel hypoxic load parameters predicted cognitive performance after adjustment for sex, age, and education. CONCLUSION: The findings validate that the AHI is not an effective indicator of cognitive performance in OSA and suggest that average oxygen saturation during sleep may be the strongest PSG predictor of cognitive decline seen in OSA. The results also underline the importance of considering age when choosing neurocognitive tests, the importance of including more than one test for each cognitive domain as most tests are not pure measures of a single cognitive factor, and the importance of including tests that cover all cognitive domains as OSA is likely to have diffuse cognitive effects.

Dynamic flexoelectric instabilities in nematic liquid crystals.

Electrohydrodynamic phenomena in liquid crystals constitute an old but still very active research area. The reason is that these phenomena play the key role in various applications of liquid crystals and due to the general interest of the physical community in out-of-equilibrium systems. Nematic liquid crystals (NLCs) are ideally representative for such investigations. Our article aims to study theoretically the linear NLCs dynamics. We include into consideration orientation elastic energy, hydrodynamic motion, external alternating electric field, electric conductivity, and flexoelectric polarization. We analyze the linear stability of the NLC film, determining dynamics of perturbations with respect to the homogeneous initial state of the NLC. For the purpose we compute eigenvalues of the evolution matrix for a period of the external alternating electric field. These eigenvalues determine the amplification factors for the modes during the period. The instability occurs when the principal eigenvalue of the evolution matrix becomes unity by its absolute value. The condition determines the threshold (critical field) for the instability of the uniform state. It turns out that one might expect various types of the instability, only partially known and investigated in the literature. Particularly, we find that the flexoelectric instability may lead to two-dimensionally space-modulated patterns exhibiting time oscillations. This type of the structures was somehow overlooked in the previous works. We formulate conditions needed for the scenario to be realized. We hope that the results of our work will open the door to a broad range of further studies. Of especial importance would be a comprehensive understanding of the role of various material parameters and nonlinear effects which is a key step for the rational design of NLCs exhibiting the predicted in this publication multidimensional oscillating in time patterns.

Unconventional Radical and Radical-Hole Site-Based Interactions in Halogen-Bearing Dimers and Trimers: A Comparative Study.

Radical (R•) and R•-hole site-based interactions are comparatively studied, for the first time, using ab initio methods. In this regard, R•-bearing molecules •XO3 (where X = Cl, Br, and I) were subjected to direct interaction with NH3 within dimeric and trimeric forms in the form of NH3···â€¢XO3/•XO3···NH3 and NH3···â€¢XO3···NH3 complexes, respectively. As confirmed by electrostatic potential analysis, the studied R•-bearing molecules •XO3 had the outstanding potentiality to interact as Lewis acid centers via two positive sites dubbed as R• and R•-hole sites. Such an observation proposed the potentiality of the considered •XO3 molecules to engage in unconventional R• and well-established R•-hole site-based interactions with Lewis bases. This was confirmed by negative interaction (E int) energies, ranging from -4.93 to -19.89 kcal/mol, with higher favorability for R• site-based interactions over the R•-hole site-based ones. MP2 energetic features furnished higher preferability for the R• site-based interactions than the R•-hole site-based ones in the case of chlorine- and bromine-bearing complexes, and the reverse was true for the iodine-bearing complexes. Moreover, elevated E int values were recorded for the NH3···â€¢XO3···NH3 trimers over the NH3···â€¢XO3 and •XO3···NH3 dimers, outlining the higher preference of the •XO3 molecules to engage in R• and R•-hole site-based interactions in the trimeric form over the dimeric one. These results might be considered a requisite linchpin for numerous forthcoming supramolecular chemistry and crystal engineering studies.

Efficacy and safety of the combination of encorafenib/cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: an AGEO real-world multicenter study.

BACKGROUND: The combination of encorafenib with cetuximab has become the standard of care in patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC) after a prior systemic therapy. This study aims to describe the efficacy and safety of encorafenib/cetuximab +/- binimetinib in patients with BRAF V600E-mutated mCRC in a real-world setting. PATIENTS AND METHODS: This retrospective study included patients with BRAF V600E-mutated mCRC who received this combination from January 2020 to June 2022 in 30 centers. RESULTS: A total of 201 patients were included, with 55% of women, a median age of 62 years, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) >1 in 20% of cases. The main tumor characteristics were 60% of right-sided primary tumor, 11% of microsatellite instability/mismatch repair deficient phenotype, and liver and peritoneum being the two main metastatic sites (57% and 51%). Encorafenib/cetuximab +/- binimetinib was prescribed in the first, second, third, and beyond third line in 4%, 56%, 29%, and 11%, respectively, of cases, with the encorafenib/cetuximab/binimetinib combination for 21 patients (10%). With encorafenib/cetuximab treatment, 21% of patients experienced grade ≥3 adverse events (AEs), with each type of grade ≥3 AE observed in <5% of patients. The objective response rate was 32.2% and the disease control rate (DCR) was 71.2%. The median progression-free survival (PFS) was 4.5 months [95% confidence interval (CI) 3.9-5.4 months] and the median overall survival (OS) was 9.2 months (95% CI 7.8-10.8 months). In multivariable analysis, factors associated with a shorter PFS were synchronous metastases [hazard ratio (HR) 1.66, P = 0.04] and ECOG-PS >1 (HR 1.88, P = 0.007), and those associated with a shorter OS were the same factors (HR 1.71, P = 0.03 and HR 2.36, P < 0.001, respectively) in addition to treatment beyond the second line (HR 1.74, P = 0.003) and high carcinoembryonic antigen level (HR 1.72, P = 0.003). CONCLUSION: This real-world study showed that in patients with BRAF V600E-mutated mCRC treated with encorafenib/cetuximab +/- binimetinib, efficacy and safety data confirm those reported in the BEACON registration trial. The main poor prognostic factors for this treatment are synchronous metastases and ECOG-PS >1.

Isolation and Characterization of Salmonella Bacteriophages as Potential Agents for Phage Therapy of Antibiotic-Resistant Intestinal Infections.

Two bacteriophages specifically active against to pathogenic strains of the Salmonella genus were isolated. The morphology of phage colonies (size, transparency, and shape of the plaque edge, and halo) and the spectrum of their lytic activity and interaction with microbial cells (adsorption rate, duration of the latency, and reproductive efficiency) were examined. Using genome-wide sequencing, we determined the taxonomic position of bacteriophages and verified the absence of unwanted genes encoding toxins, adhesins, and invasins, as well as pathogenicity islands responsible for antibiotic resistance. In addition, phage stability under different physical conditions and their productivity were studied.

Effect of Polysaccharides Isolated from Saussurea salicifolia (L.) DC on Th2-Dependent Immune Response.

The effect of polysaccharides isolated from the aboveground parts of Saussurea salicifolia (L.) DC on Th2 type immune response reactions was studied. Administration of water-soluble polysaccharides presented by arabino-galacturonans (weight average molecular weight 158.49 kDa) to mice against the background of experimental Th2 immunity reduced the severity of anaphylactic and local immediate type hypersensitivity reactions. It also suppressed the production of ovalbumin-specific IgE and IgG1 and increased the stability of mast cell membranes. The studied polysaccharide complex increased IFNγ secretion and inhibited IL-4 synthesis. These findings suggest that these polysaccharides may be considered as potential anti-allergic agents that suppress the development of allergy in its early stages.

Assessment of the Safety of Anti-Salmonella Disinfectant for Veterinary Use Based on a Cocktail of Bacteriophages.

The toxicity and safety of a veterinary anti-salmonella disinfectant based on three highly virulent bacteriophage strains (titers 1010 PFU/ml) were studied. Acute, chronic, and inhalation toxicity, as well as local irritancy of the disinfectant were evaluated on outbred white mice CD1 (n=65), Soviet chinchilla rabbits (n=20), and rats (n=20). No toxic effects of the disinfectant was observed after its intraperitoneal or intragastric administration to mice and intragastric administration to rats; in rabbits, application on the skin and eyes produced no local irritation effect. Inhalation of 10% of the disinfectant did not cause any pathologies in mice. Thus, the tests confirmed the high level of safety of the disinfectant based on a mixture of bacteriophages for use as an additional specific disinfection agent against Salmonella in veterinary and livestock facilities.

Cytologic findings in mandibular and superficial cervical lymph nodes of dogs with thyroid carcinoma.

Objective: To describe cytologic findings from mandibular and superficial cervical lymph nodes in dogs with thyroid carcinoma and to determine prognostic factors associated with lymph node metastasis. Animals: A total of 71 client-owned dogs with confirmed thyroid carcinoma that had cytologic results from at least 1 mandibular or superficial cervical lymph node between 2010 and 2020. Procedure: Medical records from 2 referral veterinary hospitals were retrospectively reviewed. Cytology of lymph nodes was reviewed for presence of metastasis by diplomates of the American College of Veterinary Pathologists. Thyroid tumor diameter and volume, tumor fixation, bilateral location, vascular invasion, and stage were recorded to determine effects on nodal metastasis. Results: A total of 154 lymph nodes (104 mandibular and 50 superficial cervical lymph nodes) from 71 dogs were cytologically evaluated, and 1/154 (0.6%) and 2/154 (1.3%) lymph nodes were noted to be definitively metastatic or probably metastatic, respectively. Given the infrequent rate of nodal metastasis (1.9% or less), statistical analysis of potential prognostic variables was not completed. Conclusion and clinical relevance: Routine lymph node cytology of mandibular and superficial cervical lymph nodes appeared to be of low yield when assessing for metastasis of canine thyroid carcinomas. The medial retropharyngeal and deep cervical lymph nodes should continue to be evaluated as they appeared to have higher metastatic rates, based on historic reports. Additional studies are needed to determine prognostic factors associated with lymph node metastasis and effects on patient survival.

Résultats cytologiques dans les ganglions lymphatiques cervicaux mandibulaires et superficiels de chiens atteints d'un carcinome thyroïdien. Objectif: Décrire les résultats cytologiques obtenus des ganglions lymphatiques mandibulaires et cervicaux superficiels chez des chiens atteints d'un carcinome thyroïdien et déterminer les facteurs pronostiques associés aux métastases ganglionnaires. Animaux: Un total de 71 chiens appartenant à des clients atteints d'un carcinome thyroïdien confirmé avec des résultats cytologiques d'au moins un ganglion lymphatique cervical mandibulaire ou superficiel entre 2010 et 2020. Procédure: Les dossiers médicaux de 2 hôpitaux vétérinaires de référence ont été examinés rétrospectivement. La cytologie des ganglions lymphatiques a été examinée pour détecter la présence de métastases par des diplomates de l'American College of Veterinary Pathologists. Le diamètre et le volume de la tumeur thyroïdienne, la fixation de la tumeur, la localisation bilatérale, l'invasion vasculaire et le stade ont été notés pour déterminer les effets sur les métastases ganglionnaires. Résultats: Au total, 154 ganglions lymphatiques (104 ganglions lymphatiques mandibulaires et 50 ganglions lymphatiques cervicaux superficiels) provenant de 71 chiens ont été évalués par cytologie, et 1/154 (0,6 %) et 2/154 (1,3 %) ganglions lymphatiques ont été notés comme définitivement métastatiques ou probablement métastatiques, respectivement. Compte tenu du taux peu fréquent de métastases ganglionnaires (1,9 % ou moins), l'analyse statistique des variables pronostiques potentielles n'a pas été complétée. Conclusion et pertinence clinique: La cytologie de routine des ganglions lymphatiques mandibulaires et cervicaux superficiels semblait être de faible rendement lors de l'évaluation des possibilités de métastases des carcinomes thyroïdiens canins. Les ganglions lymphatiques rétropharyngés médiaux et cervicaux profonds doivent continuer à être évalués car ils semblent présenter des taux métastatiques plus élevés, sur la base des rapports historiques. Des études supplémentaires sont nécessaires pour déterminer les facteurs pronostiques associés aux métastases ganglionnaires et les effets sur la survie des patients.(Traduit par Dr Serge Messier).

Weight-Based Standardized Sugammadex Dosing in Pediatrics: A Quality Improvement Initiative to Improve Compliance with Dosing Guidelines and Reduce Waste and Cost.

Methods: Sugammadex vials were fractionated into 25, 50, or 100 mg aliquots, which would be distributed to anesthesia staff by pharmacy staff in approximate 2 mg/kg of actual body weight doses (±10%). We analyzed changes in sugammadex waste and dosing practices 1/1/2019 to 3/15/2023 pre/postintervention (4/1/2021). We gauged dose appropriateness using last train of four (TOF) prior to sugammadex administration. Results: 7,889 patients 2-17 years (4,771 with documented TOF), ASA 1-4 receiving general anesthesia with a steroidal NMB medication and sugammadex reversal. Pre- and postintervention mean doses were 2.5 mg/kg (SD: 1.2) and 2.4 mg/kg (SD: 0.96), respectively. A smaller proportion of cases received standard 2 or 4 mg/kg doses (pre: 77.6 vs. post: 66.7%). Mean waste per case declined from 4.2 mg/kg (SD: 4.1) to 0.22 mg/kg (SD: 0.38). Among cases with 0 or 1 measured twitches on TOF that should receive at least 4 mg/kg, fewer received at least 3.6 mg/kg (post: 56.7% vs. pre: 66.8%), and a greater proportion received less than 2.2 mg/kg (post: 27.4% vs. pre: 20.7%). Among cases that should have received at least 2 mg/kg by TOF, the proportion of patients receiving more than 3.6 mg/kg declined from 9.5% to 5.2%. Discussion. Fractionating sugammadex vials was associated with decreases in waste, but not dose, and significant underdosing was more likely to occur. While vial fractionation could enable increased access to sugammadex and other costly medications, it may introduce unintended consequences.

Effects of Partial Replacement of Corn Grains With Mango Seed Kernel on Nutrient Digestibility, Blood Metabolites and Rumen Parameters of Growing Calves.

Fruit by-products are a sustainable and cost-effective alternative to traditional grain feed for livestock. One of the most important by-products is mango seed kernel (MSK), which can be used as a valuable energy source for feeding growing calves in the tropical and subtropical productive regions of the world. This study investigated the effect of replacing corn grains (CGs) with MSK on intake, nutrient digestibility, blood metabolites and rumen parameters. Eighteen growing male Friesian calves (200 ± 6.55 kg of body weight and 9-11 months old) were randomly assigned to three treatment groups. Three concentrate feed mixtures were formulated such that MSK replaced CG at 0%, 25% and 50%. Dry matter intake was unaffected, whereas dry matter, organic matter and fibre digestibility increased linearly (p < 0.05) with increased inclusion of MSK. Ruminal pH (p = 0.053) and total volatile fatty acid (VFA) concentration (p = 0.041) increased linearly. There was a linear decrease in cholesterol (p = 0.029) and AST (p = 0.028) levels in the blood of calves. In conclusion, this study demonstrated the positive effect of replacing 50% of CG with MSK on rumen parameters, including a higher ruminal pH and total VFA concentration, alongside higher nutrient digestibility. The dietary inclusion of mango seed can serve as a valuable and sustainable dietary component for growing calves.

Cerebrospinal fluid liquid biopsy by low-pass whole genome sequencing for clinical disease monitoring in pediatric embryonal tumors.

Background: Liquid biopsy assays that detect cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) are a promising tool for disease monitoring in pediatric patients with primary central nervous system (CNS) tumors. As a compliment to tissue-derived molecular analyses, CSF liquid biopsy has the potential to transform risk stratification, prognostication, and precision medicine approaches. Methods: In this pilot study, we evaluated a clinical pipeline to determine feasibility and sensitivity of low-pass whole genome sequencing (LP-WGS) of CSF-derived cfDNA from patients with CNS embryonal tumors. Thirty-two longitudinal CSF samples collected from 17 patients with molecularly characterized medulloblastoma (12), embryonal tumor with multilayered rosettes (2), CNS embryonal tumor, not elsewhere classified (NEC) (2), and atypical teratoid/rhabdoid tumor (1) were analyzed. Results: Adequate CSF-derived cfDNA for LP-WGS analysis was obtained in 94% of samples (30/32). Copy number variants compatible with neoplasia were detected in 90% (27/30) and included key alterations, such as isodicentric ch17, monosomy 6, and MYCN amplification, among others. Compared to tissue specimens, LP-WGS detected additional aberrations in CSF not previously identified in corresponding primary tumor specimens, suggesting a more comprehensive profile of tumor heterogeneity or evolution of cfDNA profiles over time. Among the 12 CSF samples obtained at initial staging, only 2 (17%) were cytologically positive, compared to 11 (92%) that were copy number positive by LP-WGS. Conclusions: LP-WGS of CSF-derived cfDNA is feasible using a clinical platform, with greater sensitivity for tumor detection compared to conventional CSF cytologic analysis at initial staging. Large prospective studies are needed to further evaluate LP-WGS as a predictive biomarker.

Mapping of schistosome hybrids of the haematobium group in West and Central Africa.

Hybridization of parasitic species is an emerging health problem in the evolutionary profile of infectious disease, particularly within trematodes of the genus Schistosoma. Because the consequences of this hybridization are still relatively unknown, further studies are needed to clarify the epidemiology of the disease and the biology of hybrid schistosomes. In this article, we provide a detailed review of published results on schistosome hybrids of the haematobium group. Using a mapping approach, this review describes studies that have investigated hybridization in human (S. haematobium, S. guineensis, and S. intercalatum) and animal (S. bovis and S. curassoni) schistosome species in West Africa (Niger, Mali, Senegal, Côte d'Ivoire, Benin, Nigeria) and in Central Africa (Cameroon, Gabon, Democratic Republic of Congo), as well as their limitations linked to the underestimation of their distribution in Africa. This review provides information on studies that have highlighted hybrid species of the haematobium group and the regions where they have been found, notably in West and Central Africa.

Discrimination training affects stimulus generalization in mice during Pavlovian eyeblink conditioning.

The delicate balance between discrimination and generalization of responses is crucial for survival in our ever-changing environment. In particular, it is important to understand how stimulus discrimination affects the level of stimulus generalization. For example, when we use non-differential training for Pavlovian eyeblink conditioning to investigate generalization of cerebellar-related eyelid motor responses, we find generalization effects on amount, amplitude and timing of the conditioned responses. However, it is unknown what the generalization effects are following differential training. We trained mice to close their eyelids to a 10 kHz tone with an air-puff as the reinforcing stimulus (CS+), while alternatingly exposing them to a tone frequency of either 4 kHz, 9 kHz or 9.5 kHz without the air-puff (CS-) during the training blocks. We tested the generalization effects during the expression of the responses after the training period with tones ranging from 2 kHz to 20 kHz. Our results show that the level of generalization tended to positively correlate with the difference between the CS+ and the CS- training stimuli. These effects of generalization were found for the probability, amplitude but not for the timing of the conditioned eyelid responses. These data indicate the specificity of the generalization effects following differential versus non-differential training, highlighting the relevance of discrimination learning for stimulus generalization.

Portable Acceleration of CMS Computing Workflows with Coprocessors as a Service.

Computing demands for large scientific experiments, such as the CMS experiment at the CERN LHC, will increase dramatically in the next decades. To complement the future performance increases of software running on central processing units (CPUs), explorations of coprocessor usage in data processing hold great potential and interest. Coprocessors are a class of computer processors that supplement CPUs, often improving the execution of certain functions due to architectural design choices. We explore the approach of Services for Optimized Network Inference on Coprocessors (SONIC) and study the deployment of this as-a-service approach in large-scale data processing. In the studies, we take a data processing workflow of the CMS experiment and run the main workflow on CPUs, while offloading several machine learning (ML) inference tasks onto either remote or local coprocessors, specifically graphics processing units (GPUs). With experiments performed at Google Cloud, the Purdue Tier-2 computing center, and combinations of the two, we demonstrate the acceleration of these ML algorithms individually on coprocessors and the corresponding throughput improvement for the entire workflow. This approach can be easily generalized to different types of coprocessors and deployed on local CPUs without decreasing the throughput performance. We emphasize that the SONIC approach enables high coprocessor usage and enables the portability to run workflows on different types of coprocessors.

[Neurofeedback in the treatment of cognitive impairment in patients with early cerebral small vessel disease]. / Neirotrening metodom biologicheskoi obratnoi svyazi v korrektsii kognitivnykh narushenii u bol'nykh rannei tserebral'noi mikroangiopatiei.

OBJECTIVE: To compare the effectiveness of neurofeedback (NFB) at infra-low and alpha frequencies in the treatment of cognitive impairment in patients with early cerebral small vessel disease (cSVD). MATERIAL AND METHODS: The study included 71 patients (average age 52.8±6.3 years, men 15%, women 85%) with early cSVD and 21 healthy volunteers (average age 53.2±4.8 years, men 29%, women 71%). All participants were assessed for clinical manifestations and cognitive functions, brain MRI, and EEG. cSVD patients were randomized by an envelope method with double-blind placebo control. Three groups of neurofeedback were formed: infra-low waves (n=25), alpha waves (n=22), simulated neurofeedback using EEG (placebo) (n=24). Fifteen sessions of 30 minutes were conducted 2-5 times a week. The cognitive profile and EEG were assessed immediately and 6-8 weeks after completion of the neurofeedback course. RESULTS: Patients with early cSVD had subjective (65%) and moderate (35%) cognitive impairment with predominant deviations in the components of executive brain functions (EBF). Neurofeedback using infra-low waves significantly improved EBF in the components of productivity, switching and inhibition, non-verbal delayed memory immediately after the course, maintaining the effect for at least 6-8 weeks, which was accompanied by an increase in the power (µB2) of the alpha rhythm in the occipital regions. Neurofeedback using alpha waves showed improvement in the Stroop test (interference index) in the delayed period. CONCLUSION: In patients with early cSVD and deterioration of EBF, it is preferable to conduct biofeedback neurotraining at infra-low frequencies to treat cognitive impairment and create a cognitive reserve. An increase in the power of the alpha rhythm in the occipital regions during the course can be considered a prognostic marker of its effectiveness.

The Ethanolic Extract of Polygala paniculata L. Blocks Panx1 Channels and Reduces Ischemic Brain Infarct in a Dose- and Sex-Dependent Way.

Polygala paniculata L. is a native plant from tropical America. The therapeutic potential of the hydroalcoholic extract of P. paniculata (HEPp) has been scientifically explored due to folk medicine reports on its action against several afflictions. HEPp contains several bioactive molecules with neuroprotective activities, making it a promising candidate for stroke treatment. This study used electrophysiological, biochemical, and in vivo experiments to evaluate the molecular mechanisms underlying HEPp as a neuroprotective therapy for stroke targeting Pannexin-1 (Panx1). Panx1 is a non-selective channel that opens during ischemia and contributes to neuronal death. HEPp was not toxic to cortical neurons and pre-treatment with the extract reduced neuronal death promoted by oxygen and glucose deprivation in a dose-dependent manner. Additionally, HEPp blocked Panx1 currents in a dose-dependent manner and the effect, which was shown to be partially due to rutin. Animals submitted to photothrombosis and post-treated with HEPp had reduced infarct volume, and the effective dose was lower in males (1 mg/kg) than in females (10 mg/kg). On the other hand, in Panx1 KD mice (50% Panx1 levels), the acute treatment reduced the infarct volume only in males. Upon chronic treatment with HEPp, a reduction in Panx1 protein levels was observed. The current study provides reliable evidence of the neuroprotective properties of HEPp in both in vitro and in vivo models of stroke. The underlying mechanism involves, at least in part, the inhibition of Panx1 channel function and possibly downregulation of protein levels, suppressing the secondary events that lead to apoptosis and inflammation.

Subcutaneous adipose tissue radiodensity: An emerging risk factor for severe COVID-19.

BACKGROUND: Adipose tissue radiodensity and metabolic activity may influence COVID-19 outcomes. This study evaluated the association between adipose tissue characteristics and clinical outcomes in COVID-19 patients. METHODS: Two retrospective cohorts of hospitalized COVID-19 patients were analyzed. Subcutaneous adipose tissue radiodensity (SATR) and visceral adipose tissue radiodensity were assessed by computed tomography. Fluorine-18-labelled fluorodeoxyglucose PET/computed tomography measured adipose tissue metabolic activity. Associations with mortality, length of stay, ventilation requirement, and complications were examined using regression analyses. RESULTS: High SATR was independently associated with increased mortality risk (OR: 2.70; P = 0.033), longer hospitalization (P < 0.001), higher rates of mechanical ventilation (P = 0.007), and complications: acute kidney injury (P = 0.001), secondary infection (P = 0.007), shock (P = 0.010), and pulmonary embolism (P = 0.011). SATR positively correlated with SAT glucose uptake (ρ = 0.52) and negatively with leptin levels (ρ = -0.48). CONCLUSIONS: Elevated SATR at COVID-19 diagnosis predicts disease severity and worse outcomes. SATR is a potential prognostic biomarker for acute and chronic inflammatory conditions.